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Modulation of antioxidant enzymes and programmed cell death by n-3 fatty acids

  • Antioxidant Status and Peroxidation
  • Published:
Lipids

Abstract

Studies from our laboratory indicate that n-3 (fish oil, FO) lipids at 10% (w/w) in a nutritionally adequate, semipurified diet, and supplemented with equal levels of antioxidants, extended the life span of lupus-prone (NZB/NZW)F1 (B/W) female mice as compared to n-6 (corn oil, CO) lipids. The early rise of autoimmune disease in CO-fed mice was closely linked to the loss of T-cell function. Both IL-2 production and IL-2 receptor expression were reduced due to the loss of naive T-Cells and a rise in memory T-cells. Proliferative response to both mitogens and superatigens (staphylococcal enterotoxins A and B) was higher in FO-fed 6.5-mon-old mice. These changes paralleled decreased PGE2 production by splenic cells from FO-fed mice.

Analysis of mRNA expression in different organs revealed differential effects of dietary lipids. In FO-fed, mice, transforming growth factor β1 (TGF β1) expression was decreased in kidneys, but splenic tissues had higher expression of TGF β mRNA. As TGF β promotes programmed cell death (PCD), we studied the effects of CO and FO on PCD rates in lymphocytes. Both propidium iodide staining and DNA fragmentation were elevated in lymphocytes of FO-fed mice when compared to CO-fed mice of similar age. Also, increased PCD correlated closely with increased Fas gene expression. Thus, in addition to various other antiinflammatory effects, dietary FO appears to increase PCD and prevent accumulation of self-reactive immune cells in lymphoid organs. Further studies are required to dissect the proand antiinflammatory mechanisms associated with dietary n-3 and n-6 lipids in modulating autoimmune disorders or malignancy during aging.

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Abbreviations

B/W mice:

(NZB/NZW)F1 mice

CAT:

catalase

CO:

corn oil

CTLL-2:

cytotoxic T-lymphocyte line 2

FACS:

fluorescence activated cell sorting

FO:

fish oil

GSH-Px:

glutathione peroxidase

ICAM-1:

intercellular adhesion molecule-1

IL-2:

interleukin-2

LTB4 :

luekotriene B4

MDA:

malondialdehyde

MRL/lpr mice:

MRL mouse with a lymphoroliferative (lpr) gene

PCD:

programmed cell death

PGE2 :

prostaglandin E2

PI:

propidium iodide

SLE:

systemic lupus erythematosus

SOD:

superoxide dismutase

TBARS:

thiobarbituric acid-reactive substances

TBHQ:

tert-butylhydroquinone

TGF β:

transforming growth factor β

TNF-α:

tumor necrosis factor-α

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Authors and Affiliations

  1. Department of Medicine, The University of Texas Health Science Center, 7703 Floyd Curl. Dr., 782847874, San Antonio, TX

    Gabriel Fernandes, Bysani Chandrasekar & Xianghong Luan

  2. Department of Pathology, The University of Texas Health Science Center, 7703 Floyd Curl. Dr., 782847874, San Antonio, TX

    Dean A. Troyer

Authors
  1. Gabriel Fernandes
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  2. Bysani Chandrasekar
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  3. Xianghong Luan
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  4. Dean A. Troyer
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Fernandes, G., Chandrasekar, B., Luan, X. et al. Modulation of antioxidant enzymes and programmed cell death by n-3 fatty acids. Lipids 31, S91–S96 (1996). https://doi.org/10.1007/BF02637058

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